Scintillation proximity assays (SPA), developed from the original radioimmunoassay, is a homogeneous, sensitive, fast and simple scintillation bead-based assay platform. Due to the diversification of radio-labeled ligands and of affinity tags modified on the scintillation carrier’s surface, as well as the development of scintillation recorders and liquid handling technologies, SPA has been widely used as a high throughput method for lead compound screening and biomarker detection. In this review, after a brief introduction of the principle and operation of SPA, a detailed advance of its applications in life sciences were outlined, especially on membrane proteins analysis and at the cell level analysis with detailed classical reports. Beyond that, the methods on increasing the ratios of signal/noise were also analyzed. The wide spread of SPA, especially of its innovations at the cell level research will definitely promote our comprehensive understanding of cellular system biology.